TY - JOUR
T1 - A Structure-Reactivity Relationship of the Tandem Asymmetric Dihydroxylation on a Biologically Relevant Diene
T2 - Influence of Remote Stereocenters on Diastereofacial Selectivity
AU - Gill, Daniel
AU - Male, Louise
AU - Jones, Alan M
PY - 2019/12/15
Y1 - 2019/12/15
N2 - The Sharpless asymmetric dihydroxylation (AD) finds widespread use in natural product and drug molecule syntheses, in part, due to its efficiency and predictability. However, the tandem AD of dienes is much less studied, but important in complex molecular synthesis. Herein, a biologically relevant tandem AD is reported, and several anomalies are discovered with the accepted model. These include the formation of unpredicted diastereoisomers, with matched and mismatched stereocenters contradicting the Sharpless mnemonic device. From a structural analysis of the tandem AD, we present a strategy to improve asymmetric induction in sterically hindered alkenes using double diastereodifferentiation from a 9-bond distant stereocenter. A theoretical justification for the unpredicted stereoselectivity, accounting for the influence of steric hindrance and pre-installed chirality, is proposed.
AB - The Sharpless asymmetric dihydroxylation (AD) finds widespread use in natural product and drug molecule syntheses, in part, due to its efficiency and predictability. However, the tandem AD of dienes is much less studied, but important in complex molecular synthesis. Herein, a biologically relevant tandem AD is reported, and several anomalies are discovered with the accepted model. These include the formation of unpredicted diastereoisomers, with matched and mismatched stereocenters contradicting the Sharpless mnemonic device. From a structural analysis of the tandem AD, we present a strategy to improve asymmetric induction in sterically hindered alkenes using double diastereodifferentiation from a 9-bond distant stereocenter. A theoretical justification for the unpredicted stereoselectivity, accounting for the influence of steric hindrance and pre-installed chirality, is proposed.
KW - Asymmetric dihydroxylation
KW - sharpless
KW - tandem
KW - diastereodifferentiation
KW - stereofacial selectivity
UR - http://www.scopus.com/inward/record.url?scp=85076046634&partnerID=8YFLogxK
U2 - 10.1002/ejoc.201901474
DO - 10.1002/ejoc.201901474
M3 - Article
SN - 1434-193X
VL - 2019
SP - 7568
EP - 7577
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
IS - 46
ER -